Chugai Seiyaku Kabushiki Kaisha

Jsr Corporation

Jsr Life Sciences Corporation

Nara Medical University

Tsukasa Suzuki

Takehisa Kitazawa

Tomoyuki Igawa

Atsushi Muto

Tetsuo Kojima

Zenjiro Sampei

Tetsuhiro Soeda

Chifumi Imai

Kazutaka Yoshihashi

Yukiko Nishida

Tetsuji Yamaguchi

Yuji Sano

Toshihiko Ohtomo

Hideki Adachi

Hajime Miyamoto

Midori Shima

Keiji Nogami

Hiroyuki Saito

Jun Amano

Takaki Koga

Motoaki Mizuuchi

Mei Ono

Shigehisa Nagahashi

Masahiro Takeyama

Seiki Wakui

The present inventors attempted to produce antibodies that neutralize the activity of a substance having an activity of functionally substituting for FVIII to be used for the method of measuring the reactivity of FVIII in the presence of a substance having an activity of functionally substituting for FVIII. As a result, the inventors discovered that by using the produced antibodies, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately by one-stage clotting assay based on APTT, and also that FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately by Bethesda assay based on APTT.

Antibody capable of neutralizing substance having activity alternative to function of coagulation factor VIII (FVIII)

The present invention relates to a method for assaying soluble GPC3 protein in a test sample, comprising using two different antibodies binding to different epitopes present in the N-terminal region of GPC3 protein.

Method for assaying soluble GPC3 protein

Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Methods of treatment that include the administration of bispecific antibodies

As a result of producing anti-DDR1 antibodies and conducting extensive studies on the antitumor activity thereof, antibodies that bind to the stalk domain in the amino acid sequence of human DDR1 were found to have a potent activity even when used alone compared to antibodies that bind to other domains. It was also found that the antibodies have one or more activities selected from the group consisting of: (i) an activity to suppress cell proliferation, (ii) an activity to inhibit cell migration, (iii) an activity to inhibit phosphorylation of DDR1 in cells, (iv) an activity to be taken up into cells, (v) an activity to decrease the expression level of DDR1 in cells, and (vi) an activity to decrease the expression level of TGF-&#x3b2; in cells.

Anti-DDR1 antibody having anti-tumor activity

Bispecific antibodies

The present inventors have succeeded in producing anti-AXL antibodies with specific functions. The present inventors also discovered that the antibodies have an angiogenesis-suppressive effect and an antitumor effect, and thereby completed the present invention. The anti-AXL antibodies of the present invention are useful as angiogenesis inhibitors and agents for inducing or inhibiting phosphorylation activity.

Monoclonal antibody capable of binding to anexelekto, and use thereof

For the first time, the present invention provides antibodies that enhance the generation of activated blood coagulation factor VIII. The antibodies enhance the cleavage of blood coagulation factor VIII at the Arg of position 372 and suppress the cleavage at the Arg of position 336 by recognizing and binding to the A2 domain of blood coagulation Factor VIII. Such antibodies are expected to be useful in preventing or treating diseases that develop or progress due to decrease or loss of the blood coagulation factor VIII activity, for example, hemophilia A, acquired hemophilia, and von Willebrand's disease.

Blood coagulation factor VIII activation-enhancing antibodies

The present invention provides anti-aPC antibodies that suppress the inactivation of activated protein C (aPC), and uses thereof. The present inventors screened anti-aPC antibodies, and succeeded in isolating anti-aPC antibodies comprising the activity of suppressing aPC inactivation in blood. The antibodies of the present invention can be used to maintain aPC activity by suppressing aPC inactivation, and can thus be used to sustain aPC bioactivities, such as the activity of suppressing activation of the blood coagulation system, and anti-inflammatory activity. In addition, the present invention provides uses of the antibodies of the present invention in aPC therapy for diseases such as thrombosis and sepsis. The therapeutic effect of aPC can be prolonged in treatment that uses aPC administration by allowing an antibody of the present invention to bind with aPC. The antibodies of the present invention can be used in the treatment and prevention of diseases such as thrombosis and sepsis.

Non-neutralizing anti-aPC antibodies

Growing community of inventors

Shizuoka, Japan

Tsukasa Suzuki